What is the Underlying Pathophysiology of Intrinsic Asthma (Non-Allergic Asthma, Hyper-responsive Reaction)?

Overview of Intrinsic Asthma (Adult-Onset):

• Etiology: The precise mechanisms are less understood compared to extrinsic asthma.
• Potential Triggers & Theories:
  • T-Cell Activation: Some researchers hypothesize that T cells may become inappropriately activated, causing inflammation without an allergic trigger.
  • Cold Air & Respiratory Irritants: Exercise or sudden cold exposure may irritate the respiratory tract, prompting immune responses.
  • Autonomic Nervous System Imbalance: The bronchial smooth muscles are innervated by the autonomic nervous system; an imbalance could cause excessive bronchoconstriction.

Pathophysiology & Remodeling:

• Over time, both extrinsic and intrinsic asthma lead to airway remodeling:
  • Smooth Muscle Hypertrophy: Thickening of the bronchial wall due to smooth muscle proliferation, leading to a narrowed lumen.
  • Mucous Gland Hyperplasia: Increased number and size of mucus glands, resulting in more mucus production with each attack.
  • Mucosal Edema: Swelling of the mucosa during inflammation.
• These changes make airway obstruction more persistent and severe with recurrent attacks.

Symptoms and Attacks:

• Typical signs during an attack:
  • Cough (usually dry and nonproductive due to thick mucus plugs).
  • Shortness of breath.
  • Chest tightness.
  • Wheezing from mucus plugs and bronchospasm.
  • Use of accessory muscles (sternocleidomastoid, pectoralis minor) to breathe.
• Physiological responses:
  • Hypoxia: The brain triggers faster breathing and accelerates the heart rate to deliver more oxygen.
  • Nighttime pooling: Edema and mucus can accumulate when lying down, worsening breathing difficulties.

Hemodynamic Changes:

• Pulsus Paradoxus:
  • An abnormal decrease (>10 mm Hg) in blood pressure during inspiration compared to expiration.
  • Caused by exaggerated negative intrathoracic pressure during deep inspiration, affecting cardiac filling and blood pressure regulation.

Summary:

Intrinsic asthma involves airway hyper-responsiveness that may not be allergy-driven but could involve neural or immune dysregulation. Structural airway changes worsen with recurrent attacks, increasing severity and risk of chronic airflow limitation.